Disease burden, clinical management and unmet treatment need of patients with moderate to severe atopic dermatitis; consensus statements, insights and practices from CERTADE (Central/Eastern EU, Russia, Turkiye AD Experts) Delphi panel.

Background: There is limited insight into the current disease burden and everyday clinical management of moderate-to- severe AD in Poland, Czechia, Russia, and Turkiye. Therefore, this study aimed to get information-driven insights regarding the current disease burden and clinical management of patients with moderate-to-severe AD with common and differentiating aspects of the patient journey and establish a consensus. Methods: In this modified 2-round Delphi panel, 133 questions were asked in total to 27 dermatologists. A consensus was achieved when 70% of the panel members strongly agreed or agreed (or strongly disagreed or disagreed) with an item. Statements with <40% agreement dropped from the Delphi rounds and were not repeated. Results: The results state that AD has a significant impact on the quality of life for both patients and their families with social and economic consequences in these countries. While there were significant dissimilarities regarding the current treatment approach by preference order and treatment duration among participants, there was also a high percentage of consensus on literature and guideline-based statements. Current topical therapies and the immune response modifiers were not found to be sufficient by panelists to cover the therapeutic needs of patients with moderate-to-severe AD. Moreover, panelists highlighted the significant burden of adverse events with the off-label use of currently available immunosuppressants. Conclusions: These results underlined that there is a significant disease burden with an unmet treatment need for patients with moderate-to-severe AD in Poland, Czechia, Russia, and Turkiye.

Hair Shaft Abnormalities as a Dermoscopic Feature of Mycosis Fungoides: Pilot Results.

INTRODUCTION: Diagnosis of persistent erythematous, scaly patches, or plaques can be complex since psoriasis (Ps), eczematous dermatitis (ED), and mycosis fungoides (MF) can be considered. Dermoscopy, which is a noninvasive diagnostic tool, is commonly used to examine blood vessels, scales, and background color; however, research on hair shaft evaluation in inflammatory dermatoses remains scarce. The aim of the study was dermoscopic evaluation of hair shafts in skin lesions localized on the non-scalp skin areas in patients diagnosed with MF, Ps, and ED. METHODS: This was a retrospective evaluation of 55 patients diagnosed with MF, Ps, and ED. Photographic and dermoscopic documentation of these patients and detailed medical history were evaluated. RESULTS: A total of 21 patients with MF, 21 patients with Ps, and 13 patients with ED were evaluated. The examination revealed the presence of various abnormalities of hair shafts (e.g., numerous pili torti, single pili torti, 8-shaped hairs, pigtail hairs, broken hairs, hair shafts rapidly tapered over long sections, hair shafts irregular in thickness, angulated hairs, branched hairs, the presence of trichorrhexis nodosa, and monilethrix-like hairs), yellow dots, and black dots. The presence of pili torti was found in 80% of patients with MF, compared with 16% of patients with Ps and 8% of patients with ED (p < 0.005), with multiple pili torti found only in MF patients (67%) (p < 0.005). Statistically significant differences also applied to hair shafts rapidly tapering over long sections and 8-shaped hairs, which occurred only in MF patients (p < 0.005 and p = 0.035, respectively). CONCLUSIONS: The presence of hair shaft abnormalities such as numerous pili torti, 8-shaped hairs, and hair shafts rapidly tapering over long sections is an important criterion that should be considered in the dermoscopic differentiation of the patchy/plaque mycosis fungoides and inflammatory dermatoses, such as psoriasis and eczematous dermatitis localized on the non-scalp skin areas.

Dermoscopic Nail Changes in Psoriasis, Lichen Planus, and Lichen Striatus.

Background: Onychoscopy is a noninvasive method helpful in diagnosing nail disorders. The aim of the study was to review literature on the usability of onychoscopy in nail psoriasis, nail lichen planus, and nail lichen striatus. Summary: Onychoscopic features of nail psoriasis are pitting, onycholysis with erythematous border, salmon patches, splinter hemorrhages, dotted vessels in lateral and proximal folds, and hyponychium. Onychoscopic features of nail lichen planus are onychorrhexis, onycholysis, longitudinal melanonychia, and red lunula. The literature on the usability of onychoscopy in nail lichen striatus is scarce. Keynotes: Onychoscopy facilitates evaluation of nail abnormalities compared to the clinical examination. Lunular alterations, salmon patches, erythematous border of onycholysis as well as splinter hemorrhages in nail psoriasis are better visualized with onychoscopy compared to the naked eye. Onychoscopy enhances detection of melanonychia, dyschromia, and lunular changes in nail lichen planus. Onychoscopic features are different in fingernails and toenails.

Onychoscopy (nail dermoscopy) is a noninvasive method used in diagnosing of nail disorders. In this review, we evaluated if onychoscopy may be helpful in diagnosing inflammatory nail disorders such as psoriasis, lichen planus, and lichen striatus. Nail psoriasis can be characterized with the presence of pitting, salmon patches, splinter hemorrhages, onycholysis with or without erythematous border and dilated vessels in the hyponychium on onychoscopy. Onychoscopy of nail lichen planus shows the presence of longitudinal ridging and splitting (onychorrhexis), splinter hemorrhages, longitudinal melanonychia as well as red lunula (distal part of nail matrix). The data on onychoscopy in nail lichen striatus are scarce. Onychoscopy is a helpful tool in visualization of nail abnormalities, with most of the features better visualized with onychoscopy compared to the naked eye.

Isotretinoin as a promising option in the treatment of facial papules of frontal fibrosing alopecia.

Frontal fibrosing alopecia (FFA) is a primary cicatricial alopecia characterized by hairline recession, pruritus, and facial papules (FP). Various therapies are used to stabilize disease activity and induce remission. However, FP of FFA is resistant to treatment in many cases. In this review, we searched the PubMed and Google Scholar databases to screen the published literature on treatment options for FP in the context of FFA. Overall, 12 studies were included in this review. Available literature suggests a noticeable improvement in resistant-to-treatment FP in FFA patients with oral isotretinoin. The available evidence is limited and is derived from retrospective studies and case reports/series. Systemic isotretinoin can be considered a promising therapeutic regimen for treating resistant-to-treatment FP of FFA patients. However, more extensive, well-designed studies are necessary for confirmatory evidence.

Hair Evaluation in Orthodontic Patients with Oligodontia.

Oligodontia can be isolated or syndromic, associated with other ectodermal abnormalities. The aim of the study was to perform hair examination in orthodontic patients diagnosed with oligodontia with a low clinical expression of symptoms of ectodermal origin. All available orthodontic patients diagnosed with oligodontia in the permanent dentition were enrolled. Hair examination included clinical evaluation of the patients' hair, trichoscopy, trichogram and evaluation of the hair shafts under a polarized light microscope. In total, 25 patients, 18 males and 7 females, aged 6 to 24 years were evaluated for the presence of dental and hair abnormalities. The number of congenitally absent teeth ranged from 6 to 24 teeth and diastemas, microdontia, taurodontism and altered tooth shape were found in 23 patients. Hair disorders were found in 68% of the subjects. Hypotrichosis, the heterogeneity of shaft color and loss of pigment, androgenetic alopecia, telogen effluvium, trichoschisis, pili canaliculi, trichorrhexis nodosa and pseudomoniletrix were observed. Trichoscopy and trichogram are valid non-invasive diagnostic tests which could be used to differentiate between isolated and syndromic oligodontia in patients with a low clinical expression of ectodermal symptoms.

Disease burden, clinical management and unmet treatment need of patients with moderate to severe alopecia areata; consensus statements, insights, and practices from CERTAAE (Central/Eastern EU, Russia, Türkiye AA experts) Delphi panel.

Objectives: This study aims to update the understanding of Alopecia Areata (AA) in Poland, Czechia, Russia, and Türkiye, focusing on the disease burden, clinical management, and patient journey. It seeks to establish a consensus on optimal management strategies for AA in these regions. Methods: A modified 2-round Delphi panel was conveyed with 23 Dermatologists (Russia; 4, Türkiye; 7, Poland; 6, and Czechia; 6). The Delphi questionnaire consisted of 61 statements and 43 questions designed to obtain an overall understanding of the perception and acceptance of available information regarding the care of patients with alopecia areata. Results: The study revealed that moderate-to-severe AA significantly impacts patients' and their families' QoL, consistent with previous studies. AA was found to cause more substantial impairment when additional lesions appeared in visible areas besides the scalp. Work and productivity impairment were notably higher in adults with moderate-to-severe AA. Diagnostic consensus highlighted the importance of skin biopsies and trichoscopy, while the need for more practical severity scoring systems was emphasized. Current treatments, including topical therapies, corticosteroids, and systemic immune modifiers, were deemed insufficient, highlighting the unmet medical need. Conclusion: The Delphi study underscores a significant disease burden and unmet medical needs in patients with moderate-to-severe AA. It highlights the necessity of access to novel treatments and further research to develop more effective therapies with a tolerable safety profile. The findings align with global research, emphasizing the psychosocial impact of AA and the need for standardized, effective treatment protocols.

Androgenetic Alopecia in Children and Adolescents: From Trichoscopy to Therapy.

Introduction: Pediatric androgenetic alopecia is a product of hormonal and genetic factors. The diagnosis depends on recognizing the hair loss pattern in the context of a positive family history and a typical trichoscopy. Methods: A multicenter retrospective study assessing medical data from January 2008 to January 2023 of two reference centers - one public and one private in west Mexico. Patients under 18 years old were included. The clinical features, trichoscopic findings, associated conditions, and treatment received were documented and analyzed. Results: We found 145 patients, with a mean age of 16.08 ± 1.30 years, predominantly comprising males (72%). Trichoscopy was performed on 33 patients. The main trichoscopic findings were hair shaft thickness variability in 100% of the cases, vellus hair in 85%, and single-hair units in 79%. Vitamin D deficiency was found in 84% of the cases with laboratory determination, insulin resistance in 33%, and hyperandrogenemia in 12.5%. Topical minoxidil emerged as the main treatment modality in 24% of cases, demonstrating both efficacy and tolerability. Conclusion: Pediatric androgenetic alopecia could be more prevalent than commonly perceived, potentially explained by the lower level of suspicion among medical practitioners. Distinctive trichoscopic findings offer valuable guidance for therapeutic strategies and ongoing management.

Trichoscopy of Androgenetic Alopecia: A Systematic Review.

Background: Androgenetic alopecia, the most common cause of non-scarring hair loss, is a consequence of the gradual miniaturization of the hair follicles. In the majority of male androgenetic alopecia cases, a patient's history and clinical evaluation may be sufficient to establish the diagnosis, while for women, they should be supplemented with trichoscopy. Methods: The PubMed and Scopus databases were used to collate published studies and to analyze the most typical trichoscopic findings in patients diagnosed with androgenetic alopecia. A total of 34 articles were retrieved after exclusion. Results: The most common features identified using trichoscopy included hair diameter variability (94.07% of patients), vellus hairs (66.45%) and the peripilar sign (43.27%). Others, such as the honeycomb pattern, yellow and white dots, were less relevant. Conclusions: We concluded that hair diameter variability, vellus hairs and the peripilar sign represented valuable indicators for the diagnosis of androgenetic alopecia.

Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxoedema and scleroedema.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this consensus provides clinicians with an overview of the diagnosis and treatment of scleromyxoedema and scleroedema (of Buschke).

Efficacy and Safety of Rilzabrutinib in Pemphigus: PEGASUS Phase 3 Randomized Study.

TRIAL DESIGN: Pemphigus is a rare but life-threatening autoimmune disease requiring long-term treatment that minimizes corticosteroid (CS) exposure while providing consistent disease control. The phase 2 pemphigus study of oral, reversible, covalent Bruton tyrosine kinase inhibitor rilzabrutinib demonstrated rapid and sustained efficacy with well-tolerated safety. METHODS: Adults (aged 18-80 years) were randomized 1:1 to 400 mg rilzabrutinib (n = 65) or placebo (n = 66) twice daily (with CS ≤ 0.5 mg/kg/d) for 37 weeks in the phase 3 PEGASUS study in moderate-to-severe pemphigus vulgaris/pemphigus foliaceus. RESULTS: The primary endpoint of complete remission from week 29 to week 37 with the amended endpoint CS dose ≤10 mg/d was not significant for 13 of 54 (24%) rilzabrutinib versus 10 of 55 (18%) placebo patients with PV (P = .45). Secondary endpoints showed numerical but nonsignificant improvements with rilzabrutinib (vs placebo) in reduced CS use, prolonged complete remission duration, and faster time to first complete remission. CONCLUSIONS: Overall, rilzabrutinib was well-tolerated, with similar adverse events reported in both groups. Using minimal CS dose ≤10 mg/d and excluding remote observations, the primary efficacy endpoint was not met. However, results from a prespecified sensitivity analysis using CS dose ≤5 mg/d, considering all observations, and including all patients support Bruton tyrosine kinase inhibition as a viable therapeutic approach for pemphigus.

Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program.

BACKGROUND: The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA). OBJECTIVE: The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA. METHODS: Two cohorts were analyzed: a placebo-controlled and an all-exposure cohort. Proportions and study size-adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported. RESULTS: In the placebo-controlled cohort (n = 881; median exposure: 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2-75.4% across doses versus 69.5% in the placebo group; serious AEs occurred in 0-3.2% versus 1.9% for the placebo. A total of 19 patients permanently discontinued due to AEs (5 while receiving the placebo). In the all-exposure cohort (n = 1294), median ritlecitinib exposure was 624 days [2091.7 total patient-years (PY)]. AEs were reported in 1094 patients (84.5%) and serious AEs in 57 (4.4%); 78 (6.0%) permanently discontinued due to AEs. The most common AEs were headache (17.7%; 11.9/100 PY), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (15.5%; 9.8/100 PY), and nasopharyngitis (12.4%; 8.2/100 PY). There were two deaths (breast cancer and acute respiratory failure/cardiorespiratory arrest). Proportions (IRs) were < 0.1% (0.05/100 PY) for opportunistic infections, 1.5% (0.9/100 PY) for herpes zoster, 0.5% (0.3/100 PY) for malignancies (excluding nonmelanoma skin cancer), and 0.2% (0.1/100 PY) for major adverse cardiovascular events. CONCLUSIONS: Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available). TRIAL REGISTRIES: ClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).

Dermoscopic characteristics of cutaneous larva migrans in dark skin: a study from Banjul, The Gambia.

Cutaneous larva migrans (CLM) results from hookworm larvae infestation, mainly Ancylostoma braziliense or Ancylostoma caninum. It is common in Sub-Saharan Africa, often acquired through soil contact, especially in sandy beaches, manifesting as serpiginous, erythematous and intensely pruritic tracts within the epidermis, and presenting with diverse clinical appearances. Diagnosis is mostly clinical; however, dermoscopy can enhance diagnostic accuracy and distinction from mimics. The current body of literature is deficient in its representation of dermoscopic data for CLM in Black patients. This study explores dermoscopy in nine dark-skinned patients with 16 CLM lesions. Distinctive serpiginous structureless areas displaying a range of colours, peripheral scales surrounding brown areas and brown dots were predominant features, whereas vascular characteristics were less evident. This article highlights the presence of distinct reaction patterns, including brown dots, scales, and accentuated, often disrupted brown reticular lines in addition to the characteristic winding tracts in darker skin.

Trichoscopy - a valuable tool for identifying conditions mimicking androgenetic alopecia.

Androgenetic alopecia (AGA) is the most prevalent type of hair loss in women and men. Recently, a European consensus group published guidelines for the diagnostic evaluation of AGA in men, women, and adolescents. This S1 guideline presents expert opinion-based recommendations for gender-dependent steps in the diagnostic procedure, which can easily be implemented in the daily clinical routine. For diagnosing AGA, detailed anamnesis and objective learning are not enough because there are several conditions mimicking this disease. Trichoscopy can be considered an important, non-invasive tool for diagnosing hair and scalp disorders that may have similar clinical signs to AGA.

Autoinflammatory Keratinization Diseases-The Concept, Pathophysiology, and Clinical Implications.

Recent advances in medical genetics elucidated the background of diseases characterized by superficial dermal and epidermal inflammation with resultant aberrant keratosis. This led to introducing the term autoinflammatory keratinization diseases encompassing entities in which monogenic mutations cause spontaneous activation of the innate immunity and subsequent disruption of the keratinization process. Originally, autoinflammatory keratinization diseases were attributed to pathogenic variants of CARD14 (generalized pustular psoriasis with concomitant psoriasis vulgaris, palmoplantar pustulosis, type V pityriasis rubra pilaris), IL36RN (generalized pustular psoriasis without concomitant psoriasis vulgaris, impetigo herpetiformis, acrodermatitis continua of Hallopeau), NLRP1 (familial forms of keratosis lichenoides chronica), and genes of the mevalonate pathway, i.e., MVK, PMVK, MVD, and FDPS (porokeratosis). Since then, endotypes underlying novel entities matching the concept of autoinflammatory keratinization diseases have been discovered (mutations of JAK1, POMP, and EGFR). This review describes the concept and pathophysiology of autoinflammatory keratinization diseases and outlines the characteristic clinical features of the associated entities. Furthermore, a novel term for NLRP1-associated autoinflammatory disease with epithelial dyskeratosis (NADED) describing the spectrum of autoinflammatory keratinization diseases secondary to NLRP1 mutations is proposed.